Decoy peptides effectively inhibit the binding of SARS-CoV-2 to ACE2 on oral epithelial cells

Lai Keng Loi, Cheng Chieh Yang*, Yu Cheng Lin, Yee Fun Su, Yi Chen Juan, Yi Hsin Chen, Hsiu Chuan Chang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The entry of SARS-CoV-2 into host cells involves the interaction between the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. Given that the spike protein evolves rapidly to evade host immunity, therapeutics that block ACE2 accessibility, such as spike decoys, could serve as an alternative strategy for attenuating viral infection. Here, we constructed a drug screening platform based on oral epithelial cells to rapidly identify peptides or compounds capable of blocking the spike-ACE2 interaction. We engineered short decoy peptides, 8 to 14 amino acids in length, using the spike protein's receptor-binding motif (RBM) and demonstrated that these peptides can effectively inhibit virus attachment to host cells. Additionally, we discovered that diminazene aceturate (DIZE), an ACE2 activator, similarly inhibited virus binding. Our research thus validates the potential of decoy peptides as a new therapeutic strategy against SARS-CoV-2 infections, opening avenues for further development and study.

Original languageEnglish
Article numbere22614
JournalHeliyon
Volume9
Issue number12
DOIs
StatePublished - Dec 2023

Keywords

  • ACE2
  • COVID-19
  • Decoy peptide
  • Oral epithelial cell
  • SARS-CoV-2
  • Spike protein

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